Carbapenems
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Carbapenems (synthetic β-lactams)
Imipenem/cilastatin, Meropenem, Doripenem, Ertapenem (slightly different)
• Good penetration to body fluids (including CSF)
• Elimination through kidneys
• DOSE ADJUSTMENT CRUSIAL İn kidney dysfunction
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Carbapenems
Imipenem/cilastatin
Imipenem is metabolized
in the kidney
(to a nephrotoxic product)
Cilastatin blocks the renal
dehydropeptidase that
catalyzes this rxn
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The major benefit of
ertapenem over other
carbapenems is that it has a long half-life and can be administered once daily
(caution: im application)
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For infections that are resistant to other drugs i.e. P. aeruginosa (not ertapenem)
• Mixed aerobic/anaerobic infections,
• Infections caused by ESML-producing organisms
• Intraabdominal infections
• Imipenem/cilastatin, Meropenem, Doripenem for nosocomial infections, febrile neutropenia,
What are they good for?
They may induce seizures (especially IMIPENEM)
Monobactam
Aztreonam
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Ceftolozan + Tazobactam
Ceftolozane is a novel cephalosporin antibiotic,
developed for the treatment of infections with gram- negative bacteria that have become resistant to
conventional antibiotics. It was studied for urinary tract infections, intra-abdominal infections and ventilator-
associated bacterial pneumonia
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Avibactam is a novel
broad-spectrum beta-lactamase inhibitor
The addition of avibactam to ceftazidime extends the spectrum of activity to include most Enterobacteriaceae
(including those that produce AmpC beta-lactamase, ESBL, and some K.
pneumoniae and OXA-type carbapenemases) as well as P.
aeruginosa species with high MICs to ceftazidime alone
Ceftazidime-avibactam
Meropenem-vaborbactam
Vaborbactam is a novel broad-spectrum beta- lactamase inhibitor that potently inhibits class A carbapenemases (including K. Pneumoniae
carbapenemases [KPC])
It is not active against class B or D
carbapenemases (ie, metallo-beta-lactamases and
OXA-type enzymes)
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Other Inhibitors of Cell Wall Synthesis
Vancomycin ( no oral drug available in Turkey)
• DOES NOT have beta- lactam ring
• DOES NOT bind to PBPs
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f AUC:MIC
Concentration AND Time-Dependent
• Interaction between free [AB] exposure and MIC
Prototype vancomycin (+quinolons and teicoplanin)
vancomycin
• Somewhat flexible on dosing : may reach the same fAUC by different dose as well as dosing schedule
• …
f AUC:MIC
Grudge match: Dip vs. AUC
MIC creep
• Through 5-10mg/L 15 (20)mg/L
24 saat
15x24=360mg/L
…
Conti.
infusion
https://emcrit.org/squirt/vanco/
AUC
24630mg/L AUC
24500mg/L
AUC
24370mg/L
Drennan et al. 2019. The dosing and monitoring of
vancomycin: what is the best way forward? Int J Antimicrob Agents
used in antibiotic-induced
pseudomembranous colitis (ORAL USE!!)
Teicoplanin (available only in Europe) Telavancin
Similar to vancomycin
NA in Turkey
«Flakon hazırlandıktan sonra, seçilen dozlar 250 mg
(5ml) veya 125 mg (2.5ml), 30 ml su ile seyreltilebilir ve hastaya içmesi için verilebilir veya seyreltilen madde
nazogastrik tüp ile uygulanabilir. Psödomembranöz kolit ve stafilokokal enterokolit dışındaki durumlar için
vankomisin oral olarak etkili değildir»
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Vancomycin has activity against all Gram + that have not learned to become resistant to it
Many Enterococci are resistant: VRE
People with colonized VRE (bacteria are present, but have no symptoms of an infection) do not need treatment.
Most VRE infections can be treated with
antibiotics other than vancomycin .
Laboratory testing of the VRE can determine which antibiotics will work. For people who get VRE infections in their bladder and have urinary
catheters, removal of the
catheter when it is no longer needed
can also help get rid of the infection.
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ADVERSE EFFECTS
NEPHROTOXICITY
OTOTOXICITY
Basitrasin (Thiocilline®)
• Topical only for mixed bacterial flora in surface lesions of skin or mucous membranes
• Highly nephrotoxic Cycloserine
• Exclusively to treat TB caused by M. Tuberculosis resistant to first-line agents
• Serious neurotoxicity Fosfomycin
• Single 3-g dose for uUTI Daptomycin
• Similar to vancomycin in terms of spectrum
• Skin and soft tissue infections; bacteremia and endocarditis
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